We have demonstrated in our SBIR Phase I activities that the VesiVax(r) CALV vaccine and adjuvant platform technology can be successfully used to generate formulations containing Toll-like Receptor (TLR) 3 and 7/8 agonists that elicit strong protective immunostimulatory responses in a murine pulmonary influenza challenge model. With the aid of many collaborators and support from the NIAID, we have demonstrated the ability of the VesiVax(r) system to stimulate protective immune responses in a variety of animal models and a range of antigens, using our standard TLR4 agaonist (Monophosphoryl Lipid A). Currently, there is an unmet need for novel, potent immunostimulatory adjuvant molecule (IAM) formulations, and the VesiVax(r) technology platform is designed as a highly flexible vaccine and adjuvant development system. In this revised SBIR Phase II proposal, we intend to expand our VesiVax(r) product portfolio by formulating several other IAMs and focus on further developing the VesiVax(r) formulations for commercial applications. The Specific Aims proposed in this revised SBIR Phase II application include preparation of new VesiVax(r) IAM formulations and engineering scaffold proteins for less immunogenic antigens. We will be testing these formulations, in association with various types of antigens (such as protein, haptens and VLPs), in the murine genital herpes simplex virus 2 challenge model, the murine nicotine addiction model, the murine Chagas disease model, the murine pancreatic cancer model, and the guinea pig genital herpes model.